Assessing the risk of transfusion-transmitted variant Creutzfeldt-Jakob disease: a European perspective.

Several countries have recently reassessed the international risk of variant Creutzfeldt-Jakob disease (vCJD) transmission through transfusion of blood and blood components (red blood cells, platelets and plasma) and relaxed donor deferrals based on geographic and transfusion exposure in countries formerly considered to be high risk, such as the UK. In this regard, the European Blood Alliance organised a consensus meeting of experts and involved professionals to discuss current knowledge, epidemiological data, prevention and various methods for assessing the risk of transfusion-transmitted vCJD, as well as to develop an appropriate position on possible approaches to address these challenges in Europe. Participants reached a consensus that the current risk of transfusion-transmitted vCJD associated with blood donors who either travelled to or received transfusions in the UK during the vCJD outbreak is minimal. In addressing such risks, it would be pragmatic that assessments and guidelines are developed by European expert bodies, rather than individual assessments by Member States. Regardless of the approach used, European or national, a qualitative risk assessment based on a review and analysis of available data, considering all the uncertainties and experiences of other countries, would provide crucial information to reassess blood donation strategies regarding the transfusion-associated vCJD risk.

The importance of the costoclavicular space in upper limb primary deep vein thrombosis, a study with magnetic resonance imaging (MRI) technique enhanced by a blood pool agent.

BACKGROUND: Primary upper extremity deep vein thrombosis (UEDVT) can be divided into idiopathic and effort thrombosis. Anatomical factors probably play an important role in effort thrombosis, whereas the cause remains mostly unknown in idiopathic thrombosis. OBJECTIVES: The primary objective of this study was to examine the anatomy of the subclavian region and evaluate how these factors contribute to primary UEDVT. The secondary objective was to investigate if venous compression correlates with post thrombotic syndrome (PTS). PATIENTS AND METHODS: Fifteen patients and 15 controls were enrolled in the study. The subclavian region (the costoclavicular distance and vessel area) was examined by MRI enhanced by a blood-pool contrast agent (Vasovist). The MRI was performed in two arm positions: alongside and elevated. PTS and disability were quantified with the modified Villalta score and the Disability of the Arm, Shoulder and Hand (DASH) test. RESULTS: The costoclavicular distance was significantly narrower in the UEDVT patients with the arms alongside the body but there was a significant difference only in the left arm with the arms elevated. Area of the subclavian vein: When comparing the patients non-thrombotic arm with the controls, there was a significant difference only when the arms in the supine position. Disability: There was a high correlation between DASH, Villalta and VAS but no correlation between the MRI measurement and patient's symptoms or the Villalta Score. CONCLUSION: Our results suggest that primary UEDVT is dependent on the subclavian anatomy and area of vena subclavia.

Quantitative and qualitative evaluation of plasma and urine alpha1-microglobulin in healthy donors and patients with different haemolytic disorders and haemochromatosis.

BACKGROUND: The haem-binding protein alpha(1)-microglobulin (alpha(1)m) is involved in protection against oxidative damage induced by extracellular haem/haemoglobin. A carboxy-terminally truncated form of alpha(1)m (t-alpha(1)m), formed by reactions with haemoglobin, degrades haem into a yellow-brown chromophore linked to the protein. The aim of this work was to investigate if t-alpha(1)m is present in urine from a large cohort and if urinary and plasma alpha(1)m/t-alpha(1)m concentrations are changed in patients with haemolytic disorders and haemochromatosis. METHODS: Urine and blood from patients (n=20) and a control group (n=22) were investigated for alpha(1)m and t-alpha(1)m by gel electrophoresis, Western blotting and radioimmunoassay. Data were compared to clinical chemistry data and medical records. RESULTS: Two thirds of all studied subjects displayed t-alpha(1)m in urine but the t-alpha(1)m/alpha(1)m ratio was not increased in patients. Instead, significantly elevated ratios were found in females compared to males. Patients with intravascular or extravascular haemolysis showed higher alpha(1)m, albumin and beta(2)-microglobulin/creatinine ratios in urine indicating glomerulo-tubular dysfunction. CONCLUSIONS: The demonstration of t-alpha(1)m in urine of this cohort may be of importance in quantitative clinical chemistry. Whilst impaired kidney function due to intravascular haemolysis is well-known to occur, it is an unexpected finding in a group of patients with extravascular haemolysis.

Processing of the lipocalin alpha(1)-microglobulin by hemoglobin induces heme-binding and heme-degradation properties.

Alpha(1)-microglobulin is a 26-kd protein, widespread in plasma and tissues and well-conserved among vertebrates. Alpha(1)-microglobulin belongs to the lipocalins, a protein superfamily with highly conserved 3-dimensional structures, forming an internal ligand binding pocket. The protein, isolated from urine, has a heterogeneous yellow-brown chromophore bound covalently to amino acid side groups around the entrance of the lipocalin pocket. Alpha(1)-microglobulin is found in blood both in free form and complex-bound to immunoglobulin A (IgA) via a half-cystine residue at position 34. It is shown here that an alpha(1)-microglobulin species, which we name t-alpha(1)-microglobulin (t = truncated), with a free Cys34 thiol group, lacking its C-terminal tetrapeptide, LIPR, and with a more polar environment around the entrance of the lipocalin pocket, is released from IgA-alpha(1)-microglobulin as well as from free alpha(1)-microglobulin when exposed to the cytosolic side of erythrocyte membranes or to purified oxyhemoglobin. The processed t-alpha(1)-microglobulin binds heme and the alpha(1)-microglobulin-heme complex shows a time-dependent spectral rearrangement, suggestive of degradation of heme concomitantly with formation of a heterogeneous chromophore associated with the protein. The processed t-alpha(1)-microglobulin is found in normal and pathologic human urine, indicating that the cleavage process occurs in vivo. The results suggest that alpha(1)-microglobulin is involved in extracellular heme catabolism.